WHAT IS A CLEAN ROOM 2016 - medvalpharma.co.ukmedvalpharma.co.uk/wp-content/uploads/2016/10/WHAT... · requirements. Entry of people and ... The entry to clean rooms is strictly controlled

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WHAT IS A CLEAN ROOM?

Acleanroomisanextremelysophisticatedworkenvironment,designedandbuiltwiththeexpresspurposeofprovidingahighlevelofcleanlinessforaproductionorresearchfacility.Strictly controlled in terms of:

• Cleanroomclassification• Airparticles• Pressure• Airfiltration• Temperatureandhumidity• Entryofpeopleandparts

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Clean room classification TheUKstandardsareISO14644-1(2015)andEUGMP.Air particles Thecontrolofairborneparticlesiscriticaltothecontaminationcontrolwithinthecleanroom.Pressure Pressureispositivewithinthecleanroomandhigherthanthatofthesurroundingareas,controlledtocomplywithISO14644-1.Air filtration Airfiltrationiscriticaltothecleanroomasthisremovesparticlestoahighlevel.NormallyviaH.E.P.A.(HighEfficiencyParticulateAir)filters.Temperature and humidity Temperatureandhumidityiscontrolledforcomfortandforcriticalproductionrequirements.Entry of people and parts Theentrytocleanroomsisstrictlycontrolledtoauthorisedpersonneltrainedinthedisciplineofhygieneandgowningtechniques.Partsentryisalsocriticalsoasnottocontaminatethecleanroomenvironment.

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Why do we need clean rooms? Weneedcleanroomstoensuremedicinesandcriticalcomponentswhichcanbeputintohumans(oranimals)arenotcontaminatedatproduction/dispensingstage.WealsoneedcleanroomsintheMicroelectronicindustry,toensurenoparticulateispresentintheairwherecomplexMicroelectronicdevicesareassembled.Clean rooms can be found in many industries

• Pharmaceuticals,pharmacies(hospitals),celltherapy.• Medicaldevicemanufacturers,biotechnology.• Microbiology,aerospace,avionics.• Semi-conductorassembly,waferfabrication.• Microelectronics,opticaldevices.• Fibreoptics,plasticsmoulding.• Forensicscience.• Foodindustry,brewingindustry.• Paintspraying.• Cosmetic,plasticsurgery.

Thecleanroomfacilityoffersimprovedproductqualityandreliabilitywhenmanufacturedwithinaclassifiedcleanroom.

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Definition of clean air flow Airflowpatternswithinacleanroomare;

• Non-uni-directional–turbulentflow• Uni-directional–laminarflow•

Non-uni-directional(turbulentflow)Thisairisforcedintothecleanroomandflowsfreelyinaturbulentmannertoprovideeffectiveflushingofthecleanarea.Thisairflowremovesmicronizedparticlesthroughthedesignedre-circulatoryairsystem.Airentersatceilinglevelwithexhaustairleavingatlowlevel.Uni-directionallaminarflowThisairforcesallparticlestoflowinaregimentedpath.Theuni-directionalflowcanbeverticalorhorizontalandisnormallydirectlyfromaH.E.P.A.filterorflowscreen.Uni-directionalflowdevicescanbecabinets,modulesandevenafullcleanroom.

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Non-unidirectional flow (turbulent flow)

Uni-directional (laminar flow)

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Standard for UK ISO 14644-1 (2015) Maximumconcentrationlimits(particlesperm3ofair)forparticlesequaltoorgreaterthanconsideredsizesbelow(valuesuptothreesignificantfigures).ISO 14644-1 (2015)

Class 0.1 um 0.2 um 0.3 um 0.5 um 1 um 5.0 um

ISO1 10 d d d d e

ISO2 100 24 10b d d e

ISO3 1000 237 102 35b d e

ISO4 10000 2370 1020 352 83b e

ISO5 100000 23700 10200 3520 832 def

ISO6 1000000 237000 102000 35200 8320 293

ISO7 c c c 352000 83200 2930

ISO8 c c c 3520000 832000 29300

ISO9 c c c 35200000 8320000 293000

EU GMP ORANGE GUIDE

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PARTICLES Particulatecontaminationismeasuredbytheunitsmicrometreormicronandissignifiedasµandµgm1µgisthirtyninemillionthsofaninch.OrOnemillionthofametre.Thecontrolofparticulatecontaminationismeasuredinmicronsandingeneraliscompliantwithoneormoreofthestandardsclassification.

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Particle size example Ahumanhaironendmagnifiedtoa1000timeslargerNon-viableNon-livingparticles

100 microns

10 microns ViableLivingorganisms5 microns

• .5 microns

Mostparticulatecontaminationormostparticlepenetratingsizesarebetween0.3µmand0.5µm.Viable(living)organismswhicharemostlybacteriarangefrom0.5µmto5µmandareusuallyfoundincolony-formingunits.Virusesrangefrom0.003to0.05µm.

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Bacteria particle Smallerparticleswillgathertogethertoforma“raft”uponwhichbacteriamayprosper.Apercentageofthesebacteriawouldbepathogenic.Particulatebyitselfiscapableofproducinganembolism.Thisisanobviousdangertoacleanroomorasepticfacility,producinginjectableorparentaldrugs.Operator contamination Operatorcontaminationgeneratesmorethan50%ofparticleswithinacleanroom.Humancontaminationisofbothviableandnon-viableparticulatecontamination.

• 90%ofmicrobespectrumwithinthecleanroomiscomposedofstaphylococcimicrococciofhumanorigin.

• Anoperatoratrestshedsaround250,000particlesof>0.5micronperminuterisingbyafactorofthreeorfourwheninmotion.

• Bacteriacarryingcellsreleasedfromamaleoperatoraverageasmuchas5,000particlesperminute.

• Operatorsshedacompleteskinevery20workingdays.

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UN-GOWNED OPERATOR CONTAMINATION Operators shed

Particulate

SkinflakesEyelashesCosmeticsTobacco

Operators produce

Chemicalandorganicmatter

Sodium,magnesiumCalciumOraleffluviaIron

Operators generate

Biological

BacteriaVirusesPathogens

Operators outer clothing street generate

Highlevelsofparticulate

SiliconedustFibresCelluloseNylonWool

Cosmetics Lipsticksheds 1,000,000,000>0.5µmparticlesBlushersheds 1,600,000,000>0.5µmparticlesPowdersheds 1,300,000,000>0.5µmparticlesEyeshadowsheds 3,300,000,000>0.5µmparticles

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Controlling contamination Controllingcontaminationwithinacleanroomiscriticaltomaintainingitsclassificationandalsotoprotecttheproductorprocess,whichisbeingproduced.Bygowningandensuringoperatorsunderstandtheneedforentryprocedurescontaminationcanbecontrolled.Contaminationcanbebyparticulateorelectrostaticdischarge.Tocontrol/combatcontaminationtotheproduct/processadditionalminiclassifiedcleanenvironmentscanbeintroducedwithinthecleanroom.Oftentheseminiclassifiedenvironmentsareofahigherqualityairclassthanthegeneralroomenvironment.Example:Uni-directionallaminarflowcabinet.

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Clean room principles for entry Cleanroomoperatorsshouldfullyunderstandtheneedforacorrectentrydiscipline.Cleanroomoperatorsshouldbecleanandhealthy.Theyshouldnotentercleanroomswithouthavingagoodlevelofpersonalhygieneandshouldnotenteriffeelingunwell.

Personal hygiene

Medical health

Wash/bathefrequently

Beawareofallergies

Shampoohairfrequently

Beawareofrespiratorydisorders

Wearcleanundergarmentsdaily

Beawareofskinrashes

Wearcleanouterwearregularly

Beawareofspots

Avoidscratching

Beawareofdiseases

Shavedaily(male)

Beawareofmentalphobias

Keephairundercontrol

Donotenterifunsure

Strict No’s for a clean room operative

• Nocosmetics• Nojewellery• Noeatingofdrinking• Nopaper• Nohighheelshoes• Nouncleanpeople

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Clean room disciplines AllcleanroomsshouldhaveastrictEntry/ExitS.O.P.forallstafftoviewandcomplywith:In general:

• Wearcleanroomspecifiedclothing• Wearovershoes• Weargloves• Wearhaircover• Wearfacemasksasrequired• Wearglasses/gogglesasrequired• Usetackymats

Differentclassesofcleanroomsrequiredifferentlevelsofclothing;themorecriticaltheoperationorprocess,thehigherthelevelofclothingrequiredtocontaincontamination.Summary:

• Noeatingorsmokingorchewing• Wearprotectiveclothing• Keeptalktoaminimum• Nevercombhair• Neverapplycosmetics• Keeppocketsempty• Keeppaperout• EntryalwaysthroughChangeRoom• UnderstandS.O.P.forentry• WashhandsasperS.O.P.• Removeouterstreetclothing(ifrequired)• Ensuredoorsareclosedandnotwedgeopen• Donottakeanythingintothecleanroomthatisnotrequired• Smokersshouldrinsewithmouthwashbeforeentering• Entryofparts/toolsshouldbeunderastrictcleanpolicy• AirlocksshouldbesegregatedasInorOut• DonotExitviaAirlock,alwaysuseExitChange.

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Cleaning and maintenance Thecleaningofcleanroomsiscriticaltocontrolcontamination.ArigorousS.O.P.forcleaningshouldbeusedandallcleaningmaterialsvalidatedpriortouse.Maintenanceofcleanroomsshouldtakeintoconsiderationthecontaminationitmaygenerate,generalengineeringshutdownsrequirefullcleandownoncompletion.Validation testing TocomplywithISO14644-1(2015)andEUGMPClassrequirements,thecleanroomwillrequireindependentvalidationtestingtocomplywithISO14644-2andISO14644-3.Validationtestingisastatutoryrequirementforclassification.

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Useful publications list

• ISO14644-1• ISO14644-2• ISO14644-3• ISO14644-4• EUGMPOrangeGuide#• www.s2c2.co.ukCleanRoomSocietyforContaminationControl• HTM05-03HealthandTechnicalMemorandum• ISPEBaselinePharmaceuticalEngineeringGuide.